A new perspective on the significance of the Ranotsara shear zone in Madagascar

The Ranotsara shear zone in Madagascar has been considered in previous studies to be a >350-km-long, intracrustal strike-slip shear zone of Precambrian/Cambrian age. Because of its oblique strike to the east and west coast of Madagascar, the Ranotsara shear zone has been correlated with shear zones in southern India and eastern Africa in Gondwana reconstructions. Our assessment using remote sensing data and field-based investigations, however, reveals that what previously has been interpreted as the Ranotsara shear zone is in fact a composite structure with a ductile deflection zone confined to its central segment and prominent NW-SE trending brittle faulting along most of its length. We therefore prefer the more neutral term "Ranotsara Zone”. Lithologies, tectonic foliations, and axial trace trajectories of major folds can be followed from south to north across most of the Ranotsara Zone and show only a marked deflection along its central segment. The ductile deflection zone is interpreted as a result of E-W indentation of the Antananarivo Block into the less rigid, predominantly metasedimentary rocks of the Southwestern Madagascar Block during a late phase of the Neoproterozoic/Cambrian East African Orogeny (c. 550-520Ma). The Ranotsara Zone shows significant NW-SE striking brittle faulting that reactivates part of the NW-SE striking ductile structures in the flexure zone, but also extends along strike toward the NW and toward the SE. Brittle reactivation of ductile structures along the central segment of the Ranotsara Zone, confirmed by apatite-fission track results, may have led to the formation of a shallow Neogene basin underlying the Ranotsara plain. The present-day drainage pattern suggests on-going normal fault activity along the central segment. The Ranotsara Zone is not a megascale intracrustal strike-slip shear zone that crosscuts the entire basement of southern Madagascar. It can therefore not be used as a piercing point in Gondwana reconstruction

The role of the Ranotsara Zone in southern Madagascar for Gondwana correlations

The Precambrian basement of southern Madagascar was reworked at high-grade metamorphic conditions during the East African Orogen (EAO of Stern, 1994) that formed during assembly of Gondwana in late Neoproterozoic/early Paleozoic times. At the end of the EAO, Madagascar is generally thought to be sandwiched between southern India and eastern Africa. Constraints on its paleoposition are often inferred from similarities in structural features on now dispersed continental fragments, in particular high-strain zones. Major zones with (sub)vertical foliation planes can be traced over hundreds of kilometres in southern Madagascar and have been interpreted as major vertical ductile shear zones (e.g. Windley et al. 1994; Martelat, 1998). The NW–SE trending Ranotsara Zone (dashed rectangle in Fig. 1) is regarded as an intracrustal mega strike-slip shear zone with a sinistral sense of shear that formed at the end of the Proterozoic (e.g. Nicollet, 1990; de Wit et al., 2001). A large number of studies have used the Ranotsara Zone to propose Gondwana reconstructions. The Ranotsara Zone has been correlated with various ductile shear zones in southern India, e.g. with the Bhavani Shear Zone or the Moyar Shear Zone (Katz & Premoli, 1979), the Palghat-Cauvery Shear Zone (de Wit et al., 1995), the Karur-Kamban- Painavum-Trichur Shear Zone (de Wit et al., 2001; Ghosh et al. 2004) or with the Achankovil Shear Zone (Windley et al., 1994; Martelat, 1998). Within Madagascar, the Ranotsara Zone has been correlated along strike with the more N–S trending Bongolava Zone in central-western Madagascar (Hottin 1976), and the Bongolava- Ranotsara Zone has been further traced into the Surma Shear Zone (Windley et al. 1994) and its along-strike continuation, the Aswa Shear Zone in eastern Africa (Müller 2000). Chetty (2003) suggested that the Ranotsara Zone is not only a mega shear zone, but also a terrane boundary separating a region with Archean crust to the north from a region with Neoproterozoic crust to the south. Our remote sensing and field studies of southern Madagascar indicate that the Ranotsara Zone is neither a major terrane boundary nor an intracrustal mega strike-slip shear zone and therefore can not be used as a ‘piercing point’ in Gondwana reconstructions...conferenc

Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer

Hsulf-1 is a newly identified enzyme, which has the ability to decrease the growth of hepatocellular, ovarian, and head and neck squamous cell carcinoma cells by interfering with heparin-binding growth factor signaling. Since pancreatic cancers over-express a number of heparin-binding growth factors and their receptors, the expression and function of this enzyme in pancreatic cancer was analyzed. RESULTS: Pancreatic cancer samples expressed significantly (22.5-fold) increased Hsulf-1 mRNA levels compared to normal controls, and Hsulf-1 mRNA was localized in the cancer cells themselves as well as in peritumoral fibroblasts. 4 out of 8 examined pancreatic cancer cell lines expressed Hsulf-1, whereas its expression was below the level of detection in the other cell lines. Stable transfection of the Hsulf-1 negative Panc-1 pancreatic cancer cell line with a full length Hsulf-1 expression vector resulted in increased sulfatase activity and decreased cell-surface heparan-sulfate proteoglycan (HSPG) sulfation. Hsulf-1 expression reduced both anchorage-dependent and -independent cell growth and decreased FGF-2 mediated cell growth and invasion in this cell line. CONCLUSION: High expression of Hsulf-1 occurs in the stromal elements as well as in the tumor cells in pancreatic cancer and interferes with heparin-binding growth factor signaling

Human inflammatory bowel disease does not associate with Lawsonia intracellularis infection

BACKGROUND: There is increasing evidence that bacterial infection of the intestinal mucosa may contribute to the pathogenesis of inflammatory bowel diseases (IBD). In pigs, an obligate intracellular bacterium, Lawsonia intracellularis (LI), was shown to cause proliferative enteropathy (PE) of which some forms display histological and clinical similarities to human IBD. Since LI-similar Desulfovibrio spp. may infect human cells, we hypothesized that LI might be associated with the development of human IBD. RESULTS: In human intestinal tissue samples, PCR using LLG, 50SL27, LSA and strictly LI-specific 16SII primers, yielded either no amplicons or products with weak homology to human genomic sequences. Sequencing of these amplicons revealed no specificity for LI. However, amplification of DNA with less specific 16SI primers resulted in products bearing homology to certain Streptococcus species. These 16SI-amplified products were present in healthy and diseased specimens, without obvious prevalence. CONCLUSION: LI is not associated with the pathogenesis of UC or CD. Whether an immunologic response to commensal bacteria such as streptococci may contribute to the chronic inflammatory condition in IBD, remained to be determined

Faulting, basin formation and orogenic arcuation at the Dinaric–Hellenic junction (northern Albania and Kosovo)

The Dinaric–Hellenic mountain belt bends where two fault systems transect the orogen: (1) the dextral Shkoder-Peja Transfer Zone (SPTZ), active sometime between the Late Cretaceous and middle Eocene; (2) the Shkoder-Peja Normal Fault (SPNF), which accommodated NW–SE directed orogen-parallel extension. The SPTZ dextrally offsets the Dinaric–Hellenic nappes by ~ 75 km, a displacement attributed to reactivation of an Early Mesozoic rift transfer zone in the Adriatic margin during Paleogene subduction of the Pindos Ocean. This subduction involved an initial counter-clockwise rotation of the Hellenides with respect to the Dinarides around a pole at the NW end of the Budva–Krasta–Cukali–Pindos Basin. The SPNF overprints the SPTZ and is a composite structure comprising five fault segments: four of them (Cukali–Tropoja, Decani, Rožaje, Istog) were active under ductile-to-brittle conditions. They downthrow the West Vardar Ophiolite in the hanging wall. The Cukali–Tropoja and Decani segments exhume domes with anchizonal-to-greenschist-facies metamorphism in their footwalls. These structures formed during a first-phase of extension and clockwise rotation, whose Paleocene age is constrained by cross-cutting relationships. A second extensional phase was accommodated mainly by the fifth (Dukagjini) segment of the SPNF, a subsurface normal fault bordering syn-rift, mid-late Miocene clastic and lacustrine sediments in the Dukagjini Basin (DB) that are sealed by Plio-Pleistocene strata. This later phase involved subsidence of Neogene basins at the Dinaric–Hellenic junction coupled with accelerated clockwise oroclinal bending. The driving force for clockwise rotation is thought to be bending and rollback of the untorn part of the Adriatic slab beneath the Hellenides

Effects of STI571 (gleevec) on pancreatic cancer cell growth

BACKGROUND: Pancreatic cancer is an aggressive malignancy characterized by low responsiveness to chemotherapy and radiotherapy. This resistance is partly due to the overexpression of several tyrosine kinase receptors and their ligands. STI571 has specific activity in inhibiting c-kit, PDGF and Abl receptor tyrosine kinases and has proven successful in the treatment of CML and GIST patients. Here, we investigated the potential role of STI571 in pancreatic cancer. RESULTS: The GI(50 )of STI571 as well as the effects of STI571 on growth factor actions in pancreatic cell lines were analyzed using the MTT assay. FACS analysis using Annexin and PI staining was performed to study cell cycle, apoptosis, and cell death. Western blot analysis was carried out to investigate MAP kinase and receptor tyrosine kinase phosphorylation. STI571 inhibited cell proliferation in pancreatic cancer cell lines with GI(50 )concentrations ranging from 17 to 31.5 microM. EGF, IGF-1, and FGF-2 but not PDGF exerted growth stimulatory effects in pancreatic cancer cell lines. STI571 only partly blocked these effects on cell growth, and did not abrogate growth factor-induced receptor and MAPK phosphorylation. CONCLUSION: Our data demonstrate that STI571 inhibits pancreatic cancer cell growth with high GI50 concentrations through tyrosine-kinase receptor independent pathways. The clinical application of STI571 in pancreatic cancer is therefore rather doubtful

Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer.</p> <p>Methods</p> <p>B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells.</p> <p>Results</p> <p>B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018).</p> <p>Conclusion</p> <p>We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer.</p